New drug W18 is '10,000 times more powerful than morphine'

Previous Topic Next Topic
 
classic Classic list List threaded Threaded
12 messages Options
Reply | Threaded
Open this post in threaded view
|

New drug W18 is '10,000 times more powerful than morphine'

Soliado
http://www.independent.co.uk/news/world/americas/w18-new-drug-is-10000-times-more-powerful-than-morphine-a7013661.html

As I researched W18 on the Internet, I found a number of sites offering this drug for sale. The companies classified W18 as a "research drug." The sites all appeared to be for Chinese companies. As of today's date, 09/17/2016, the synthetic drug W18 is not illegal to possess in the U.S.  

Samuel Osborne-Independent.co.uk

A new drug considered to be 10,000 times more powerful than morphine has hit the market in the US after being discovered in Canada.

The synthetic opiate W-18 is a psychoactive substance and opioid similar to heroin, but is 100 times more powerful than fentanyl.

It is now making its way to the US at a time when fentanyl-related deaths in Canada continue to rise.

From 2009 to 2014, there were an estimated 655 deaths in Canada linked to fentanyl overdoses, according to Vice News.

While fentanyl is now a controlled substance, W-18 is yet to be prohibited in Canada or the US. It was made illegal in Sweden on 26 January, 2016.

W-18 was first seized in Canada in August 2015, when police in Calgary seized a shipment of 110 pills thought to contain fentanyl, CBC news reported.

A small number of those pills were actually found to contain traces of W-18.

Over the last year, larger quantities of W-18 have been found in other locations across Canada and the US.

In March, a man in Florida was found to have two and a half pounds of W-18 when he was arrested for selling fentanyl pills, the Sun Sentinel reported.

The drug is believed to be created in labs in China and then sold online.

It was originally developed as a painkiller by scientists at the University of Alberta in 1981.

After being deemed too strong, it was never picked up by pharmaceutical companies and was largely forgotten about.

The effect of W-18 on humans is largely unknown, because the drug was only ever tesed on lab mice.

It is currently unclear how addictive it may be, or what potential side-effects it may cause.
Reply | Threaded
Open this post in threaded view
|

Re: New drug W18 is '10,000 times more powerful than morphine'

Cuidado
10,000 times more powerful than morphine?  You would think that would be enough to simply kill a person.  Wtf
Reply | Threaded
Open this post in threaded view
|

Re: New drug W18 is '10,000 times more powerful than morphine'

Siskiyou_Kid
You dilute one milligram in a measured amount of water and then use a pipet with measurements to make dosages that are nonlethal and manageable.

The problem is that a lot of dealers are junkies, and they fuck up when they are high, and users end up dead.
Those that say, don't know. Those that know, don't say.
Reply | Threaded
Open this post in threaded view
|

Re: New drug W18 is '10,000 times more powerful than morphine'

Chimera
In reply to this post by Soliado
It looks like W-18 may not be an opioid after all:


Jul 28, 2016 @ 01:12 PM

W-18 Is Not A Super-Potent Designer Opioid As Originally Believed

David Kroll,  Contributor



A street drug feared to be stronger than any opioid known to science turns out not be an opioid at all. W-18, an experimental pain medicine first developed at the University of Alberta in Edmonton in the 1980s, doesn’t even appear to provide relief in animal pain models.

The findings appeared July 24, 2016 in a preprint report (PDF) in bioRxiv (pronounced “Bioarchive”), a non-peer-reviewed resource of Cold Spring Harbor Laboratories designed to rapidly disseminate critical research findings. The authors include scientists from the National Institute of Drug Abuse, the University of North Carolina at Chapel Hill, Memorial Sloan Kettering Cancer Center and the Scripps Research Institute.

The comprehensive study not only showed the lack of opioid effects of W-18 or a related chemical called W-15. They showed that human or mouse metabolites of the chemicals had no effect on human or mouse opioid receptors. More surprisingly, a receptorome-wide screen showed no substantial effect of the compounds or metabolites on any psychoactive drug receptor. The study marks a rare case where a potentially lethal drug of abuse is likely to be far less of a public health risk than originally believed.




Where did the hysteria come from?

The research team picked up on media reports on law enforcement drug seizures since last summer in western Canada and south Florida, where W-18 was found alone and in batches of fentanyl, an already powerful opioid responsible for over 270 Canadian deaths.

The heightened concern derived from a 1984 patent on W-18 and 30 of its chemical relatives that described the drug as 10,000 times more potent than morphine. By extension, that made W-18 100 times more potent than fentanyl. Beyond the predicted risk to users, it meant that even handling or accidentally inhaling the powdered chemical could be lethal.

This led law enforcement officials, Health Canada and the media to initially–and mistakenly–describe the drug as an opioid. But the comparison to morphine in the patent was made in a relatively non-specific mouse model of pain where other classes of pain relievers (analgesics) and unrelated drugs show effectiveness. The drug has never been evaluated in humans.

The then-graduate student who made the compounds told me in April that he and the two other inventors had never tested the chemicals as opioids and had only preliminary evidence that the painkilling effects could be reversed by the opioid antagonist naloxone (Narcan; Adapt Pharma). But no further work on W-18 or its relatives was published by the inventors or other researchers since the patent.

Over the last several months, three of the authors told me that the chemical structure of W-18 raised their suspicions because it stood out from any other known opioid. Part of the molecule could be seen to be related to fentanyl. But W-18 contains a group of atoms called a sulfonamide group that’s more commonly associated with the first known antibiotics.

Michael Baumann, PhD, Director of NIDA’s Designer Drug Research Unit, says that his monitoring of surveillance reports on W-18′s appearance in street drugs and forensic reports led him to reach out to opioid pioneer Gavril Pasternak, MD, at MSKCC and UNC’s Bryan Roth, MD, PhD, who runs the National Institute of Mental Health’s Psychoactive Drug Screening Program (PDSP). Roth’s PDSP was already investigating W-18′s ability to bind any of a battery of neurochemical receptors, including 326 receptors in the G-protein family (GPCR) that are known to be “druggable.”

Authentic W-18 first became available to researchers from Cayman Chemical Company in Ann Arbor, Michigan, a provider of wide-ranging verified chemicals and services in animal and human health. Cayman CEO Kirk Maxey, MD, told me that they started selling W-18 after forensic laboratories reported the appearance of not only the drug, but also other new chemical relatives not included in the 1984 patent.

That’s right: After Canada placed W-18 in its highest classification of controlled substances and the U.S was considering the same, clandestine chemists were already making new, related chemicals to evade the law.


W-18 isn’t an opioid or analgesic of any kind

Although the bioRxiv report is a preprint that has yet to be subject to peer-review, I looked at it with the eye of someone with 25 years of peer-review experience in others areas of biochemical pharmacology, granted in cancer rather than neuroscience. So I’m including a bullet-point summary that may be more technical than needed for the typical Forbes reader, but I also know that a lot of you are scientists and physicians.

Typical of many preprints, the report contains minor typographical errors that typical spellchecking software would miss but would be corrected in the editorial process. But scientifically, it’s a tour de force of in vitro (test tube) and in vivo (whole-animal) experiments with thorough attention to repetition and replication of the findings.

An overview of what W-18 and W-15 don’t do is:

    Neither W-18 nor W-15 binds to cloned human or mouse opioid receptor of the mu, kappa, delta or nociceptin subtypes (at concentrations up to 10,000 nanomolar).


    Neither W-18 nor W-15 affects the pathway by which opioid effects are communicated from the outside to the inside of receptor-expressing cells (via either G-protein-dependent inhibition of cAMP production or G-protein-independent translocation of beta-arrestin), with only non-specific effects at very high concentrations.

    Neither W-18 not W-15 affect the effectiveness of strong opioid agonists at the four receptor subtypes (via allosteric modulation).

    Neither W-18 not W-15 exhibit stimulatory activity at any of 326 druggable G-protein-coupled neurochemical receptors.

    A mixture of W-18 metabolites produced with either mouse or human liver enzymes show no binding to any of three cloned opioid receptor subtypes (nociceptin receptor not done).

    Neither W-18 nor W-15 show any analgesic activity in two mouse models of pain nor do they induce the characteristic opioid effect of tail raising greater than 45 degrees (Straub tail).

However, W-18 and W-15 do show some modest, non-opioid effects that would be either inconsequential or may present health risks depending how much of the chemical might be used by people:

    W-18 and/or W-15 show some weak binding to some serotonin (5-HT2A, 5-HT-2B, 5-HT2C and 5-HT6) and benzodiazepine receptors (BZP and PBR).

    W-15 was a weak antagonist (blocker) of serotonin at 5-HT2 receptors.

    W-18 and W-15 showed weak binding to A1-adenosine, alpha2-adrenergic and cannabinoid CB2 receptors but were not agonists (stimulators) at any of the receptors.

    W-18 and W-15 show some binding to the cardiac potassium channel, hERG, indicating they may cause heart rhythm disturbances at high doses (but this was not investigated further). However, the authors wrote that the potential for cardiac arrhythmias “needs to be understood by both first responders and people abusing the compound[s].”

    An in silico computer model to fit W-18 to known 3D receptor structures showed only a weak affinity for histamine H3 receptors.

    While the mouse studies showed no analgesic activity, the compounds induced the animals to burrow. However, the burrowing activity was not reversible by the opioid antagonist naloxone. It’s not clear what the burrowing behavior indicates.

So while the team showed conclusively that W-18 and W-15 are not opioids in any way, shape or form, we’re left with the mystery of why the original researchers found strong activity of these compounds in the animal pain model used in the 1980s. Since that work was only in the patent and no further work was done on the compounds, I’d place greater confidence in the more extensive work by four laboratory groups that’s presented here.

Funding for the study came from existing NIH grants (NIDA and NIMH) to Gav Pasternak, Bryan Roth and Scripps drug metabolism expert Michael Cameron, PhD. Dr. Baumann’s Designer Drug Research Unit is supported by intramural funds from NIDA. The authors indicate no financial conflicts of interest.

The first author of the report is Xi-Ping Huang from MSKCC. Other authors not mentioned in this article are: Tao Che, PhD and Thomas J. Mangamo, PhD at UNC-Chapel Hill; and Valerie Le Rouzic, BS, Ying-Xian Pan, MD, PhD, and Susruta Majumdar, PhD at MSKCC.

The full report can be accessed at bioRxiv.



http://www.forbes.com/sites/davidkroll/2016/07/28/w-18-is-not-a-super-potent-designer-opioid-as-originally-believed/2/#53720f8b1944

Reply | Threaded
Open this post in threaded view
|

Re: New drug W18 is '10,000 times more powerful than morphine'

Cuidado
Those little blue pills in the picture are roxy 30s not fentanyl.  I used to be madly addicted to those thats why I know.  
Reply | Threaded
Open this post in threaded view
|

Re: New drug W18 is '10,000 times more powerful than morphine'

durrr
Banned User
There is no legit "fentynal pills", they come in the form of many "legit" pills except they are made with fentynal and pill presses in someone's garage or lab instead of from the pharmacy. In canada the most common "fentynal pill" comes in the form of Oxy 80s.
Reply | Threaded
Open this post in threaded view
|

Re: New drug W18 is '10,000 times more powerful than morphine'

Cuidado
Those look like legit roxy 30s to me in the picture but who knows.  After googling fentanyl i noticed most of the pills do in fact look like the oxy80s with that dark green color like you said.
Reply | Threaded
Open this post in threaded view
|

Re: New drug W18 is '10,000 times more powerful than morphine'

Chimera
If those are Roxys, then they're oxycodone, not fentanyl! The author of that article didn't do his due diligence, did he?

I didn't even know fentanyl came in pills. I thought it was just injectable, patch, lozenge (like cough drop, dissolve in mouth), a sort of sponge? on a little stick you suck on. But I guess, I don't see why not pills!

******

I think you're right, Cuidado! I went to RxList.com to their Pill Identifier, and put in "M" in the Imprint, "Blue" in the Color, and "Round" in the Shape. Here's what I found:

Oxycodone!



SMH at the author.
Reply | Threaded
Open this post in threaded view
|

Re: New drug W18 is '10,000 times more powerful than morphine'

durrr
Banned User
Those are the only PHATMACEUTICAL ways of dispensing fentynal that you get perscribed by a doctor and pick up at a pharmacy. On the street it comes in allmost any form imaginable.... Knockoff pills like I said, powder, blotters (somewhat resembling acid I guess). And then there's all the patches etc. That are floating around from people selling their scripts.
Reply | Threaded
Open this post in threaded view
|

Re: New drug W18 is '10,000 times more powerful than morphine'

Cuidado
In reply to this post by Chimera
Thats why were here Chimera..lol =p
Reply | Threaded
Open this post in threaded view
|

Re: New drug W18 is '10,000 times more powerful than morphine'

Chimera


       
Reply | Threaded
Open this post in threaded view
|

Re: New drug W18 is '10,000 times more powerful than morphine'

Chimera
In reply to this post by durrr
Yes, durrr, you are SO right. I guess I should have mentioned that that's what I meant. I really very naive when it comes to most street drugs. I know a little about the usual ones you try in college lol like weed, acid, shrooms, but that's about it, except for what I've researched.

In other words, I have a lot of book knowledge but not very much real world knowledge! So I really appreciate the people on BB who are willing to share what they know with us goofs.